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الكتاب الذي بين يدينا يقدم لنا نبذة هامة عن تاريخ وسيرة مارتن لوثر كرجل إصلاحي، حيث عمد المؤلف إلى الحديث عن البيئة التي نشأ فيها وعمل فيها وشكل أفكاره والمراحل الفكرية التي مر بها، ومن هم الزملاء الذين ساعدوه، ثم كيف تحول إلى مسيرة الإصلاح ومعارضة أفكار الكنيسة، ويحدثنا عن المعارضين والمؤيدين لأطروحات مارتن لوثر، ويركز على ملامح التحول الإصلاحي الذي حققه وجهود الإصلاح على المستوى الديني أولا، حيث قدم ما عرف فيما بعد بإنجيل لوثر أو المسيحية الجديدة. كما تناول الإصلاح السياسي الذي تبع هذا الجانب الديني، وغير ذلك من المحاور الهامة.

The vast majority of the world population is infected with at least one member of the human herpesvirus family. Herpes simplex virus (HSV) infections are the cause of cold sores and genital herpes as well as life-threatening or sight-impairing disease mainly in immunocompromized patients, pregnant women and newborns. Since the milestone development in the late 1970s of acyclovir (Zovirax), a nucleosidic inhibitor of the herpes DNA polymerase, no new non-nucleosidic anti-herpes drugs have been introduced. Here we report new inhibitors of the HSV helicase-primase with potent in vitro anti-herpes activity, a novel mechanism of action, a low resistance rate and superior efficacy against HSV in animal models. BAY 57-1293 (N-[5-(aminosulfonyl)-4-methyl-1,3-thiazol-2-yl]-N-methyl-2-[4- (2-pyridinyl)phenyl]acetamide), a well-tolerated member of this class of compounds, significantly reduces time to healing, prevents rebound of disease after cessation of treatment and, most importantly, reduces frequency and severity of recurrent disease. Thus, this class of drugs has significant potential for the treatment of HSV disease in humans, including those resistant to current medications.

Rationale and objective Agonists of α7 nicotinic acetylcholine receptors (nAChRs) may have therapeutic potential for the treatment of cognitive deficits. This study describes the in vitro pharmacology of the novel α7 nAChR agonist/serotonin 5-HT 3 receptor (5-HT 3 R) antagonist N -[(3 R )-1-azabicyclo[2.2.2]oct-3-yl]-6-chinolincarboxamide (EVP-5141) and its behavioral effects. Results EVP-5141 bound to α7 nAChRs in rat brain membranes ( K i  = 270 nM) and to recombinant human serotonin 5-HT 3 Rs ( K i  = 880 nM) but had low affinity for α4β2 nAChRs ( K i  > 100 μM). EVP-5141 was a potent agonist at recombinant rat and human α7 nAChRs expressed in Xenopus oocytes. EVP-5141 acted as 5-HT 3 R antagonist but did not block α3β4, α4β2, and muscle nAChRs. Rats trained to discriminate nicotine from vehicle did not generalize to EVP-5141 (0.3–30 mg kg −1 , p.o.), suggesting that the nicotine cue is not mediated by the α7 nAChR and that EVP-5141 may not share the abuse liability of nicotine. EVP-5141 (0.3–3 mg kg −1 ) improved performance in the rat social recognition test. EVP-5141 (0.3 mg kg −1 , p.o.) ameliorated scopolamine-induced retention deficits in the passive avoidance task in rats. EVP-5141 (1 mg kg −1 , i.p.) improved spatial working memory of aged (26- to 32-month-old) rats in a water maze repeated acquisition task. In addition, EVP-5141 improved both object and social recognition memory in mice (0.3 mg kg −1 , p.o.). Conclusions EVP-5141 improved performance in several learning and memory tests in both rats and mice, supporting the hypothesis that α7 nAChR agonists may provide a novel therapeutic strategy for the treatment of cognitive deficits in Alzheimer's disease or schizophrenia.

Rationale and objective Agonists of α7 nicotinic acetylcholine receptors (nAChRs) may have therapeutic potential for the treatment of cognitive deficits. This study describes the in vitro pharmacology of the novel α7 nAChR agonist/ serotonin 5-H[T.sub.3] receptor (5-H[T.sub.3]R) antagonist N-[(3R)-1azabicyclo[2.2.2]oct-3-yl]-6-chinolincarboxamide (EVP5141) and its behavioral effects. Results EVP-5141 bound to α7 nAChRs in rat brain membranes ([K.sub.i]=270 nM) and to recombinant human serotonin 5H[T.sub.3]Rs ([K.sub.i] = 880 nM) but had low affinity for α4β2 nAChRs ([K.sub.i] > 100 µM). EVP-5141 was a potent agonist at recombinant rat and human α7 nAChRs expressed in Xenopus oocytes. EVP-5141 acted as 5-H[T.sub.3]R antagonist but did not block α3β4, α4β2, and muscle nAChRs. Rats trained to discriminate nicotine from vehicle did not generalize to EVP-5141 (0.3-30 mg [kg.sub.-1], p.o.), suggesting that the nicotine cue is not mediated by the α7 nAChR and that EVP5141 may not share the abuse liability of nicotine. EVP5141 (0.3-3mg [kg.sup.-1]) improved performance in the rat social recognition test. EVP-5141 (0.3 mg [kg.sup.-1], p.o.) ameliorated scopolamine-induced retention deficits in the passive avoidance task in rats. EVP-5141 (1 mg [kg.sup.-1],i.p.) improved spatial working memory of aged (26- to 32-month-old) rats in a water maze repeated acquisition task. In addition, EVP-5141 improved both object and social recognition memory in mice (0.3 mg [kg.sup.-1], p.o.). Conclusions EVP-5141 improved performance in several learning and memory tests in both rats and mice, supporting the hypothesis that a7 nAChR agonists may provide a novel therapeutic strategy for the treatment of cognitive deficits in Alzheimer's disease or schizophrenia. Keywords α7 nAChR agonist. Radioligand binding * Xenopus oocytes * Social recognition * Object recognition * Passive avoidance * Morris water maze * Working memory * Abuse liability * EVP-5141

Rationale and objective: Agonists of alpha 7 nicotinic acetylcholine receptors (nAChRs) may have therapeutic potential for the treatment of cognitive deficits. This study describes the in vitro pharmacology of the novel alpha 7 nAChR agonist/serotonin 5-HT sub(3) receptor (5-HT sub(3)R) antagonist N-[(3R)-1-azabicyclo[2.2.2]oct-3- yl]-6-chinolincarboxamide (EVP-5141) and its behavioral effects. Results: EVP-5141 bound to alpha 7 nAChRs in rat brain membranes (K sub( i )=270 nM) and to recombinant human serotonin 5-HT sub(3)Rs (K sub( i )=880 nM) but had low affinity for alpha 4 beta 2 nAChRs (K sub( i )>100 mu M). EVP-5141 was a potent agonist at recombinant rat and human alpha 7 nAChRs expressed in Xenopus oocytes. EVP-5141 acted as 5-HT sub(3)R antagonist but did not block alpha 3 beta 4, alpha 4 beta 2, and muscle nAChRs. Rats trained to discriminate nicotine from vehicle did not generalize to EVP-5141 (0.3-30 mg kg super(-1), p.o.), suggesting that the nicotine cue is not mediated by the alpha 7 nAChR and that EVP-5141 may not share the abuse liability of nicotine. EVP-5141 (0.3-3 mg kg super(-1)) improved performance in the rat social recognition test. EVP-5141 (0.3 mg kg super(-1), p.o.) ameliorated scopolamine-induced retention deficits in the passive avoidance task in rats. EVP-5141 (1 mg kg super(-1), i.p.) improved spatial working memory of aged (26- to 32-month-old) rats in a water maze repeated acquisition task. In addition, EVP-5141 improved both object and social recognition memory in mice (0.3 mg kg super(-1), p.o.). Conclusions: EVP-5141 improved performance in several learning and memory tests in both rats and mice, supporting the hypothesis that alpha 7 nAChR agonists may provide a novel therapeutic strategy for the treatment of cognitive deficits in Alzheimer's disease or schizophrenia.

Agonists of [alpha]7 nicotinic acetylcholine receptors (nAChRs) may have therapeutic potential for the treatment of cognitive deficits. This study describes the in vitro pharmacology of the novel [alpha]7 nAChR agonist/serotonin 5-HT^sub 3^ receptor (5-HT^sub 3^R) antagonist N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-6-chinolincarboxamide (EVP-5141) and its behavioral effects. EVP-5141 bound to [alpha]7 nAChRs in rat brain membranes (K ^sub i^=270 nM) and to recombinant human serotonin 5-HT^sub 3^Rs (K ^sub i^=880 nM) but had low affinity for [alpha]4[beta]2 nAChRs (K ^sub i^>100 [mu]M). EVP-5141 was a potent agonist at recombinant rat and human [alpha]7 nAChRs expressed in Xenopus oocytes. EVP-5141 acted as 5-HT^sub 3^R antagonist but did not block [alpha]3[beta]4, [alpha]4[beta]2, and muscle nAChRs. Rats trained to discriminate nicotine from vehicle did not generalize to EVP-5141 (0.3-30 mg kg^sup -1^, p.o.), suggesting that the nicotine cue is not mediated by the [alpha]7 nAChR and that EVP-5141 may not share the abuse liability of nicotine. EVP-5141 (0.3-3 mg kg^sup -1^) improved performance in the rat social recognition test. EVP-5141 (0.3 mg kg^sup -1^, p.o.) ameliorated scopolamine-induced retention deficits in the passive avoidance task in rats. EVP-5141 (1 mg kg^sup -1^, i.p.) improved spatial working memory of aged (26- to 32-month-old) rats in a water maze repeated acquisition task. In addition, EVP-5141 improved both object and social recognition memory in mice (0.3 mg kg^sup -1^, p.o.). EVP-5141 improved performance in several learning and memory tests in both rats and mice, supporting the hypothesis that [alpha]7 nAChR agonists may provide a novel therapeutic strategy for the treatment of cognitive deficits in Alzheimer's disease or schizophrenia.[PUBLICATION ABSTRACT]

Agonists of α7 nicotinic acetylcholine receptors (nAChRs) may have therapeutic potential for the treatment of cognitive deficits. This study describes the in vitro pharmacology of the novel α7 nAChR agonist/serotonin 5-HT3 receptor (5-HT3R) antagonist N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-6-chinolincarboxamide (EVP-5141) and its behavioral effects.RATIONALE AND OBJECTIVEAgonists of α7 nicotinic acetylcholine receptors (nAChRs) may have therapeutic potential for the treatment of cognitive deficits. This study describes the in vitro pharmacology of the novel α7 nAChR agonist/serotonin 5-HT3 receptor (5-HT3R) antagonist N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-6-chinolincarboxamide (EVP-5141) and its behavioral effects.EVP-5141 bound to α7 nAChRs in rat brain membranes (K i  = 270 nM) and to recombinant human serotonin 5-HT3Rs (K i  = 880 nM) but had low affinity for α4β2 nAChRs (K i  > 100 μM). EVP-5141 was a potent agonist at recombinant rat and human α7 nAChRs expressed in Xenopus oocytes. EVP-5141 acted as 5-HT3R antagonist but did not block α3β4, α4β2, and muscle nAChRs. Rats trained to discriminate nicotine from vehicle did not generalize to EVP-5141 (0.3-30 mg kg(-1), p.o.), suggesting that the nicotine cue is not mediated by the α7 nAChR and that EVP-5141 may not share the abuse liability of nicotine. EVP-5141 (0.3-3 mg kg(-1)) improved performance in the rat social recognition test. EVP-5141 (0.3 mg kg(-1), p.o.) ameliorated scopolamine-induced retention deficits in the passive avoidance task in rats. EVP-5141 (1 mg kg(-1), i.p.) improved spatial working memory of aged (26- to 32-month-old) rats in a water maze repeated acquisition task. In addition, EVP-5141 improved both object and social recognition memory in mice (0.3 mg kg(-1), p.o.).RESULTSEVP-5141 bound to α7 nAChRs in rat brain membranes (K i  = 270 nM) and to recombinant human serotonin 5-HT3Rs (K i  = 880 nM) but had low affinity for α4β2 nAChRs (K i  > 100 μM). EVP-5141 was a potent agonist at recombinant rat and human α7 nAChRs expressed in Xenopus oocytes. EVP-5141 acted as 5-HT3R antagonist but did not block α3β4, α4β2, and muscle nAChRs. Rats trained to discriminate nicotine from vehicle did not generalize to EVP-5141 (0.3-30 mg kg(-1), p.o.), suggesting that the nicotine cue is not mediated by the α7 nAChR and that EVP-5141 may not share the abuse liability of nicotine. EVP-5141 (0.3-3 mg kg(-1)) improved performance in the rat social recognition test. EVP-5141 (0.3 mg kg(-1), p.o.) ameliorated scopolamine-induced retention deficits in the passive avoidance task in rats. EVP-5141 (1 mg kg(-1), i.p.) improved spatial working memory of aged (26- to 32-month-old) rats in a water maze repeated acquisition task. In addition, EVP-5141 improved both object and social recognition memory in mice (0.3 mg kg(-1), p.o.).EVP-5141 improved performance in several learning and memory tests in both rats and mice, supporting the hypothesis that α7 nAChR agonists may provide a novel therapeutic strategy for the treatment of cognitive deficits in Alzheimer's disease or schizophrenia.CONCLUSIONSEVP-5141 improved performance in several learning and memory tests in both rats and mice, supporting the hypothesis that α7 nAChR agonists may provide a novel therapeutic strategy for the treatment of cognitive deficits in Alzheimer's disease or schizophrenia.

The biggest snake, the anaconda, can grow to be more than 25 feet long and to weigh 400 pounds. The smallest mammal, the Etruscan shrew, is little enough to sleep in a teaspoon. And the tiny flea can jump 130 times its own height.

Uses the book entitled \"Biggest, Strongest, Fastest\" by Steve Jenkins to provide animal facts of interest to students, which in turn become the basis for other applications of mathematics. By using themselves as a unit of measure, students have a real-world connection to the problem. This method also helps to demonstrate that even careful measurements are approximations. (AIM)

Targeting specific RNA sequences with small molecules has promising applications for the development of cell permeable probes that can selectively interfere with RNA function and could lead to novel therapeutics acting at sites of RNA protein interactions or interferine with catalytic events involving RNA. Aminoglycoside antibiotics provide the largest class of lead structures found in nature to develop such RNA binders. They target a variety of sites within the ribosomal RNA of bacteria and interfere with the catalytic function of the ribosome. To gain insight into the RNA recognition properties of aminoglycosides, the interaction with one of their natural targets, the ribosomal A-site decoding region, has been studied with a series of model RNA hairpins. A new analytical method to measure small molecule-RNA binding based on surface plasmon resonance (SPR) was developed for these studies. It was found that in particular neomycin B and related aminoglycosides bind the A-site model RNA with high specificity and nanomolar affinity. This contrasts with the lack of specificity observed for the interaction of neomycin B with another putative RNA target, the Rev Responsive Element (RRE). The structures of naturally occurring aminoglycosides were examined in search of general RNA recognition motifs. This led to the identification of hydroxyamines as a new recognition motif for phosphodiesters and the Hoogsteen face of guanosine. Model studies in DMSO showed that the 1,3-hydroxyamine motif is particularly suitable for the strong complexation of phosphodiesters. Using this motif as a core structure, a parallel solution phase approach was developed for the construction of combinatorial libraries of small molecules that target RNA.